The molecular mechanisms of RNA polymerase II termination remain poorly understood. mRNA 3' end processing is coupled to termination, and deregulation of this processing step results in human disease. The long-term objective of this project is to characterize the role of co-transcriptional processing factors in RNA 3' end processing and pol II transcriptional termination. The aims of this proposal are 1: to determine factors involved in mammalian poly(A) site dependent pol II termination, and 2: to investigate the role of the elongation factor Spt5 on pol II 3' end processing and termination. We will conduct a genome wide RNAi screen designed to identify new factors required for pol II termination in human cells. Variations on this assay might further be used to identify factors involved in alternative poly(A) site choice observed in certain cancers. PUBLIC HEALTH RELEVANCE: There are a growing number of human diseases, including cancer, that are characterized by incorrect or alternate 3' end formation of gene transcripts. mRNA 3' end processing is coupled to RNA polymerase termination. With this project I hope to determine the molecular mechanisms of transcriptional termination, and thereby expand upon our understanding of these diseases.